Expert Point of View: Eleni Efstathiou, MD, PhD

Apart from predicting resistance to androgen receptor–directed therapies, this work paves the way for liquid biopsies to identify other predictors of resistance.

—Eleni Efstathiou, MD, PhD

The magic of this research is that it requires a liquid biopsy [circulating tumor cells in the blood]—a simple blood collection,” said Eleni Efstathiou, MD, PhD, Associate Professor at The University of Texas MD Anderson Cancer Center, Houston, commenting on the study presented by Antonarakis and colleagues at the ASCO Annual Meeting. “Apart from predicting resistance to androgen receptor (AR)-directed therapies, this work paves the way for liquid biopsies to identify other predictors of resistance.”

Supportive Findings

Dr. Efstathiou is involved in research on AR variants using tissue-based biopsies, which are invasive. She noted that the findings of Dr. Antonarakis and colleagues are in line with observations from experimental data and a recent report of a tissue-based study she conducted in men with bone metastatic castration-resistant prostate cancer associating primary resistance to enzalutamide with AR-V7 presence in tumor biopsies.

The presence of AR-V7 in circulating tumor cells could help in making treatment decisions. “[If this work is validated], you would obviously not opt to treat that patient with enzalutamide or abiraterone,” she said. “We don’t want to waste time on treatments that don’t work.”

Dr. Efstathiou noted that experimental data suggest that AR-V7 may also predict resistance to taxane-based chemotherapies, but this needs further study. “This research also paves the way for research on therapies directed to AR-V7 and other variants on the N terminus of the AR receptor,” she noted.

Another piece of evidence suggesting that the presence of AR-V7 predicts resistance in general, is that patients who converted from AR-V7–negative to AR-V7–positive over the course of Dr. Antonarakis’ study had worse outcomes than those who remained AR-V7–negative throughout the study.

Other Uses

“The fact that some patients convert also means that the blood test could be used at baseline and then throughout treatment to anticipate the emergence of resistance,” she added.

Dr. Efstathiou said that the blood assay used in this study achieves a higher yield of circulating tumor cells than other currently available tests. “The blood test needs to be prospectively validated in a broader group of patients and in larger numbers to better understand its performance. CLIA certification will be required to assure cross-study uniformity,” she noted.

If the assays perform well in heterogeneous patient populations, it will then find clinical utility and be used to select patients for treatment with enzalutamide or abiraterone and guide changes in therapy, she said. ■

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